rs780590493
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PM4_Supporting
The NM_032043.3(BRIP1):c.1687_1689del(p.Asp563del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.000000684 in 1,461,768 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. D563D) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
BRIP1
NM_032043.3 inframe_deletion
NM_032043.3 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 5.34
Genes affected
BRIP1 (HGNC:20473): (BRCA1 interacting helicase 1) The protein encoded by this gene is a member of the RecQ DEAH helicase family and interacts with the BRCT repeats of breast cancer, type 1 (BRCA1). The bound complex is important in the normal double-strand break repair function of breast cancer, type 1 (BRCA1). This gene may be a target of germline cancer-inducing mutations. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PM4
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Nonframeshift variant in NON repetitive region in NM_032043.3. Strenght limited to Supporting due to length of the change: 1aa.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BRIP1 | NM_032043.3 | c.1687_1689del | p.Asp563del | inframe_deletion | 12/20 | ENST00000259008.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BRIP1 | ENST00000259008.7 | c.1687_1689del | p.Asp563del | inframe_deletion | 12/20 | 1 | NM_032043.3 | P2 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
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Cov.:
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GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251380Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135862
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GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461768Hom.: 0 AF XY: 0.00000138 AC XY: 1AN XY: 727178
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GnomAD4 genome ? Cov.: 32
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Nov 22, 2018 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 02, 2022 | The c.1687_1689delGAT variant (also known as p.D563del) is located in coding exon 11 of the BRIP1 gene. This variant results from an in-frame GAT deletion at nucleotide positions 1687 to 1689. This results in the in-frame deletion of an aspartic acid at codon 563. This amino acid position is well conserved in available vertebrate species. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital | Feb 06, 2024 | - - |
Familial cancer of breast;C1836860:Fanconi anemia complementation group J Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 16, 2024 | This variant, c.1687_1689del, results in the deletion of 1 amino acid(s) of the BRIP1 protein (p.Asp563del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs780590493, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with BRIP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 234459). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Oct 17, 2019 | Not observed at a significant frequency in large population cohorts (Lek 2016); In-frame deletion of 1 amino acid in a non-repeat region; In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge - |
Computational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at